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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊台鴻(Tai-Horng Young) | |
| dc.contributor.author | Che -Yuan Cheng | en |
| dc.contributor.author | 鄭哲淵 | zh_TW |
| dc.date.accessioned | 2021-06-08T06:22:31Z | - |
| dc.date.copyright | 2006-08-01 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-31 | |
| dc.identifier.citation | 1. 衛生署全國衛生統計資訊網（Health and National Health Insurance Annual Stastics Information Service）：民國93-94年國人主要死因統計資料（http://www.doh.gov.tw/stastic/index.htm）
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Z., Richard M., L’Hocine Y., Flow cytometric analysis of macrophage response to ceramic and polyethylene particles: Effects of size, concentration, and composition.,Journal of Biomedical Materials Research, 41(1998)600-607 31. Mao H.Q., Roy K, Troung-Le V.L., Janes K.A., Lin K.Y., Wang Y, August J.T., Leong K.W., Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency, J. Control. Rel. 70 (2001) 399-421 32. Leiden/Amsterdam Center for Drug Research.2001. Chitosans for gene delivery. Advanced Drug Delivery Reviews 52 (2001) 145-150 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25639 | - |
| dc.description.abstract | 子宮頸癌是目前台灣女性的十大死因之一，根據2006年衛生署的資料，我國在2005年共有874位女性因子宮頸癌死亡，每十萬名女性的死亡率為 7.8%，是導致女性因癌症而死亡的第五位。近年的研究中指出，導致子宮頸癌的主要因素是女性經由性交而感染“人類乳突病毒”(Human Papilloma Virus, HPV)，造成子宮頸或陰道的細胞產生病變。目前對於子宮頸癌的治療，仍停留在早期發現早期治療的階段。而新興的預防醫學中，DNA疫苗是個現今被廣泛討論也較具有成效的方法。
本研究的主要目的是希望找出奈米級的高分子粒子，以取代奈米金粒子做為子宮頸癌DNA疫苗的載體，並希望能夠找出這個系統對於提升體T細胞免疫效果的最適條件。實驗中藉由將腫瘤細胞上的特定DNA(E7)作為抗原，並結合calreticulin(CRT)，接著利用高分子奈米粒子做為DNA載體，製成DNA疫苗。此DNA疫苗便具有抗原特異性與抗血管生成的特性，且具有疫苗與免疫治療的效果，由於載體採用高分子粒子也可降低DNA疫苗的成本。再本研究同時也探討高分子奈米粒子的粒徑大小做為DNA載體對DNA疫苗的影響 。 在本研究中，首先我們先以PMMA、PS、UHMWPE、PCL和Chitosan等五種不同特性的奈米粒子，和五種不同粒徑大小的PMMA奈米粒子，來做為子宮頸癌DNA疫苗載體。由測定細胞激素TNF-α的實驗中顯示以PMMA 4做為DNA載體，對於刺激巨噬細胞造成免疫反應的效果最強。而由動物實驗部分我們可以發現以PMMA 4奈米粒子做為DNA載體，在老鼠體內所呈現的免疫效果最佳。由以上實驗結果我們可以發現，以高分子粒子做為DNA疫苗的載體是一可行的方式。 | zh_TW |
| dc.description.abstract | In Taiwan, cervical cancer is one of the most common causes of death among women. As to the cancers, cervical cancer stands the fifth place and caused 874 women to die last year. The estimated mortality is 7.8/100,000 woman per year. Recent researches have indicated that HPV is the leading cause of cervical cancer. This is a virus that spreads most commonly by sexual contacts, leading to the pathological changes of the cervix or the vagina. Till now, we have no efficient treatments to this cancer. However, in the developing preventive medicine, DNA vaccine is considered a more practical treatment.
In this study, we wanted to find more suitable nanoparticle to change the nanogold as vectors of DNA vaccine for cervical cancer. We explored the linkage of CRT to a model tumor antigen, human papilloma virus type-16 (HPV-16)E7, for the development of a DNA vaccine. This vaccine is antigen-specific and antiangiogenesis and has the effects of both vaccine and immune treatment. Because we used nanoparticle as the vectors, the costs were down dramatically. Then we explored the influences of the different particle size to DNA vaccines. We used PMMA, PS, UHMWPE, PCL, and Chitosan as cervical cancer DNA vaccine vector .In the analysis of TNF-α, PMMA 4 is the best DNA vector to massively stimulate macrophages and induce immune responses. In animal models, PMMA 4 as a DNA vector also can in mice. Result of this experiment, we can to believe it is a possible way to use polymer particle as DNA vaccine vector. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T06:22:31Z (GMT). No. of bitstreams: 1 ntu-95-R93548033-1.pdf: 897453 bytes, checksum: d2286a95dc999ce8395f15f1fe738388 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄
中文摘要……………………………………………………………….....I Abstract..……………………………………………………………..…III 誌謝……………………………………………………………………..IV 目錄…………………………………………………...…………...……VI 表目錄…………………………………………………..………………IX 圖目錄…………………………………………………………………...X 第一章 序論..............................................................................................1 1-1前言..................................................................................................1 1-2 HPV病毒（Human Papilloma Virus）...........................................2 1-3 DNA疫苗發展簡介 …………...…………………………………3 第二章 文獻回顧 ....................................................................................7 2-1 DNA疫苗的作用原理 ..................................................................7 2-2 DNA疫苗載體 …………………………………………………...9 2-3 DNA疫苗的接種方式 ………………………………………….11 2-4細胞激素（cytokine）與巨噬細胞的作用...................................11 2-5 CRT/E7………………………..…………………………………14 2-6子宮頸癌疫苗的發展與研究…………………………………...15 第三章 實驗............................................................................................17 3-1實驗流程........................................................................................17 3-2實驗藥品........................................................................................17 3-3實驗儀器........................................................................................18 3-4 試劑配製.......................................................................................20 3-5 實驗方法.......................................................................................23 3-5.1 PMMA乳膠顆粒的合成........................................................26 3-5.2轉化率的測定.........................................................................26 3-5.3 PMMA 5、PCL奈米粒子製備................................................29 3-5.4 Chitosan奈米粒子製備 ……...…………………….………30 3-5.5 PS奈米粒子製備………………...………………….………31 3-5.6 UHMWPE的製備..................................................................32 3-5.7材料的透析.............................................................................34 3-5.8粒徑測定.................................................................................35 3-5.9穿透式電子顯微鏡（Transmission Electron Microscopy）..35 3-5.10電性測定（Zeta potential）..................................................36 3-5.11細胞培養...............................................................................36 3-5.12 MTT assay…………………………………………………37 3-5.13 LDH assay………………………………………………….38 3-5.14 細胞激素（cytokine）測試.................................................39 3-5.15 大小不同奈米粒子的MTT與LDH測試..........................39 3-5.16 奈米粒子與DNA轉殖........................................................39 3-5.17高分子顆粒凝集實驗............................................................42 3-5.18動物實驗................................................................................42 第四章 結果與討論................................................................................44 4-1材料分析........................................................................................44 4-1.1高分子材料的合成.................................................................44 4-1.2粒徑分析.................................................................................45 4-1.3轉化率的測定.........................................................................46 4-1.4 DNA與奈米粒子的結合.......................................................47 4-1.5 DNA與奈米粒子轉殖後奈米粒子粒徑的穩定度...............49 4-2材料對細胞的影響........................................................................50 4-2.1MTT assay（不同材料）........................................................50 4-2.2 MTT assay（PMMA不同粒徑）..........................................51 4-2.3 CRT/E7對MTT assay的影響...............................................52 4-2.4 LDH assay…………………………………………………...52 4-2.5細胞激素（cytokine）測試....................................................53 4-3動物實驗........................................................................................56 第五章 結論..............................................................................................57 第六章 參考文獻......................................................................................59 附圖..........................................................................................................65 | |
| dc.language.iso | zh-TW | |
| dc.subject | 奈米粒子 | zh_TW |
| dc.subject | DNA | zh_TW |
| dc.subject | 子宮頸癌 | zh_TW |
| dc.subject | 疫苗 | zh_TW |
| dc.subject | cervical cancer | en |
| dc.subject | DNA | en |
| dc.subject | vaccine | en |
| dc.subject | nanoparticle | en |
| dc.title | 高分子奈米粒子做為子宮頸癌疫苗新型DNA傳輸載體之研究 | zh_TW |
| dc.title | Development of Polymer Nano-particles as Novel DNA Delivery Vehicles for Cervical Cancer Vaccination | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 婁培人(Pei-Jen Lou) | |
| dc.contributor.oralexamcommittee | 方旭偉,鄭文芳,林宏殷,李玫樺 | |
| dc.subject.keyword | DNA,子宮頸癌,疫苗,奈米粒子, | zh_TW |
| dc.subject.keyword | DNA,cervical cancer,vaccine,nanoparticle, | en |
| dc.relation.page | 82 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2006-07-31 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| 顯示於系所單位： | 醫學工程學研究所 | |
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